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Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans

Tissenbaum, Heidi A., Guarente, Leonard·2001·Nature
DOI 10.1038/35065638
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Abstract

In Caenorhabditis elegans, mutations that reduce the activity of an insulin-like receptor (daf-2) or a phosphatidylinositol-3-OH kinase (age-1) favour entry into the dauer state during larval development and extend lifespan in adults. Downregulation of this pathway activates a forkhead transcription factor (daf-16), which may regulate targets that promote dauer formation in larvae and stress resistance and longevity in adults. In yeast, the SIR2 gene determines the lifespan of mother cells, and adding an extra copy of SIR2 extends lifespan. Sir2 mediates chromatin silencing through a histone deacetylase activity that depends on NAD (nicotinamide adenine dinucleotide) as a cofactor. We have surveyed the lifespan of C. elegans strains containing duplications of chromosomal regions. Here we report that a duplication containing sir-2.1-the C. elegans gene most homologous to yeast SIR2-confers a lifespan that is extended by up to 50%. Genetic analysis indicates that the sir-2.1 transgene functions upstream of daf-16 in the insulin-like signalling pathway. Our findings suggest that Sir2 proteins may couple longevity to nutrient availability in many eukaryotic organisms.

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Crossref · 10.1038/35065638

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Citations

Cites

Research works printed but not linked: 23

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  7. Ogg, S. et al. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389, 994–999 (1997). · DOI
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Metadata

Authors
Tissenbaum, H. A., & Guarente, L.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2001-03
Volume
410
Issue
6825
Pages
227-230
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/35065638
Cited by
1,603
References
4
Language
en
Licence
www.springer.com/tdm (tdm)

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